Cue-induced drug craving is one of the most salient predictors of relapse in cocaine dependence. Functional neuroimaging studies have identified disruptions in the mesolimbic reward pathways involved in cocaine craving. The anterior cingulate cortex (ACC) is one region identified as critical in cocaine craving and motivation/drug-seeking. Thus, modulation of ACC activity has the potential to affect drug craving and relapse. Over the past year, I have participated in a study of using real-time functional magnetic resonance imaging (rtfMRI) neurofeedback from the ACC to reduce ACC activation and subjective craving in nicotine-dependent smokers. The overarching goal of the proposed research project is to modify the nicotine rtfMRI protocol and use rtfMRI feedback from the ACC to train cocaine-dependent individuals to control craving-related ACC brain activity in the face of cocaine cues. In Aim 1, I will develop a real-time visual feedback signal that indicates the magnitude of activation in individualized regions of interest during cocaine cue-related craving. The existing rtfMRI protocol that has been used to decrease self-reported craving and ACC activity in nicotine-dependent smokers will be tested and modified, as needed, using a previously developed cocaine-cue exposure task. The initial refinement of the task is critical in ensuring our ability to use the brain-computer interface to acquire ACC signal and relay the activity level to the participant. In Aim 2, I will explore the efficacy of rtfMRI feedback from th ACC in the modulation of craving-related brain activation and subjective craving in 20 cocaine-dependent individuals. Individualized neurofeedback from the ACC is predicted to lead to decreased BOLD signal in that region and decreased self-reported craving compared to instructions to reduce craving without neurofeedback. It is hypothesized that reductions in ACC activation will be correlated with decreases in self-reported craving. Moreover, whole brain analyses will provide needed insight into brain circuitry involved with successful or impaired attempts to reduce cocaine cue-induced craving both with and without feedback. The proposed study will explore the potential of an innovative, individualized approach to the treatment of cocaine dependence and pave the way for controlled clinical trials. Importantly, the proposed research addresses NIDA's strategic goal aimed at developing effective behavioral interventions to treat drug abuse and prevent relapse in addition to contributing to NIDA's treatment objective to develop the knowledge that leads to personalized or customized treatments. In sum, the proposed research directly targets a region known to be important in cocaine craving and drug-seeking with a methodology that shows promise in allowing cocaine-dependent individuals to gain control over craving-related brain activity. Through the proposed project, I will receive the intensive mentored training in rtfMRI protocol development, cue-reactivity paradigms, and clinical research in cocaine dependence which is essential to my career as an independent scientist in the area of addictions.